Chear Chai Teng, Ripen Adiratna Mat, Mohamed Sharifah Adlena Syed, Dhaliwal Jasbir Singh
Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
Gene. 2015 Apr 15;560(2):245-8. doi: 10.1016/j.gene.2015.02.019. Epub 2015 Feb 11.
Bruton's tyrosine kinase (BTK), encoded by the BTK gene, is a cytoplasmic protein critical in B cell development. Mutations in the BTK gene cause X-linked agammaglobulinemia (XLA), a primary immunodeficiency with characteristically low or absent B cells and antibodies. This report describes a five year-old boy who presented with otitis externa, arthritis, reduced immunoglobulins and no B cells. Flow cytometry showed undetectable monocyte BTK expression. Sequencing revealed a novel mutation at exon 13 of the BTK gene which created a de novo splice site with a proximal 5 nucleotide loss resulting in a truncated BTK protein. The patient still suffered from ear infection despite intravenous immunoglobulin replacement therapy. In this study, mosaicism was seen only in the mother's genomic DNA. These results suggest that a combination of flow cytometry and BTK gene analysis is important for XLA diagnosis and carrier screening.
布鲁顿酪氨酸激酶（BTK）由BTK基因编码，是一种在B细胞发育中起关键作用的胞质蛋白。BTK基因突变会导致X连锁无丙种球蛋白血症（XLA），这是一种原发性免疫缺陷病，其特征是B细胞和抗体水平低或缺失。本报告描述了一名5岁男孩，他患有外耳道炎、关节炎、免疫球蛋白降低且无B细胞。流式细胞术显示单核细胞中检测不到BTK表达。测序发现BTK基因第13外显子有一个新突变，该突变产生了一个新的剪接位点，近端有5个核苷酸缺失，导致BTK蛋白截短。尽管进行了静脉注射免疫球蛋白替代治疗，该患者仍患有耳部感染。在本研究中，仅在母亲的基因组DNA中发现了嵌合体。这些结果表明，流式细胞术和BTK基因分析相结合对于XLA诊断和携带者筛查很重要。
